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60 years of metformin use: a glance at the past and a look to the future

Cover image credit: Picture Partners / Alamy Stock Photo

To mark the 60th anniversary of the first clinical use of metformin for diabetes, Diabetologia has commissioned a series of articles on the many evolving (and controversial) aspects of metformin use. To begin, a historical overview is provided by Clifford Bailey, followed by an outline of the mechanisms of action by Rena et alSanchez-Rangel and Inzucchi go on to present data for the efficacy and safety of metformin in type 2 diabetes, for which it is the first-line therapy. In contrast, Livingstone and colleagues discuss its use in type 1 diabetes and Aroda et al present findings for its potential use for diabetes prevention. Griffin et al investigate the association between metformin and cardiovascular disease risk by conducting a meta-analysis, whilst Sam and Ehrmann and Lindsay and Loeken discuss its use in polycystic ovary syndrome and pregnancy, respectively. Metformin therapy in the ageing population is reviewed by Valencia et al, and Michael Pollak confers the non-glycaemic effects of metformin, suggesting a role for the human microbiota/gut metabolome and the immune system. Another emerging area of interest, the impact of metformin on cancer incidence and mortality, is covered by Heckman-Stoddard et al. Finally, to address the heterogeneity in response to metformin therapy, Jose Florez advises how a personalised approach may be achieved using genetic studies. In summary, this review series demonstrates how metformin shows promise in many conditions, but how long can this drug remain at the top spot?

This review set is accompanied by an editorial by Sally Marshall60 years of metformin use: what we have learnt and what we have yet to discover

Metformin: historical overview

Clifford J. Bailey

The mechanisms of action of metformin

Graham Rena, D. Grahame Hardie, Ewan R. Pearson
Metformin: clinical use in type 2 diabetes

Metformin: clinical use in type 2 diabetes

Elizabeth Sanchez-Rangel, Silvio E. Inzucchi
A new perspective on metformin therapy in type 1 diabetes

A new perspective on metformin therapy in type 1 diabetes

Rachel Livingstone, James G. Boyle, John R. Petrie, on behalf of The REMOVAL Study Team

Metformin for diabetes prevention: insights gained from the Diabetes Prevention Program/Diabetes Prevention Program Outcomes Study

Vanita R. Aroda, William C. Knowler, Jill P. Crandall, Leigh Perreault, Sharon L. Edelstein, Susan L. Jeffries, Mark E. Molitch, Xavier Pi-Sunyer, Christine Darwin, Brandy M. Heckman-Stoddard, Marinella Temprosa, Steven E. Kahn, David M. Nathan, for the Diabetes Prevention Program Research Group

Metformin use in pregnancy: promises and uncertainties

Robert S. Lindsay, Mary R. Loeken

Impact of metformin on cardiovascular disease: a meta-analysis of randomised trials among people with type 2 diabetes

Simon J. Griffin, James K. Leaver, Greg J. Irving

Metformin and ageing: improving ageing outcomes beyond glycaemic control

Willy Marcos Valencia, Ana Palacio, Leonardo Tamariz, Hermes Florez
Repurposing metformin for the prevention of cancer and cancer recurrence

Repurposing metformin for the prevention of cancer and cancer recurrence

Brandy M. Heckman-Stoddard, Andrea DeCensi, Vikrant V. Sahasrabuddhe, Leslie G. Ford
The pharmacogenetics of metformin

The pharmacogenetics of metformin

Jose C. Florez

Metformin therapy for the reproductive and metabolic consequences of polycystic ovary syndrome

Susan Sam, David A. Ehrmann

The effects of metformin on gut microbiota and the immune system as research frontiers

Michael Pollak